Pain is defined as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage.”35 Pain is one of the most prevalent and expensive medical problem in the United States, with an estimated 100 million Americans living with some level of pain, more than the estimates affected by cancer, heart disease, and diabetes.13,15 Although each individual experiences pain at some point, older adults are in general at a higher risk of suffering from chronic pain.20 Musculoskeletal pain is associated with decreased quality of life and restrictions in activities of daily living (ADLs), instrumental activities of daily living (IADLs), and mobility.8,10,20 Studies have shown that the prevalence of pain ranges from 24% to 72% among older adults, with highest prevalence in non-Hispanic whites (31%) compared with non-Hispanic blacks (26%) and Hispanics (18%).3,33
Hispanics are the fastest growing group of older adults in the United States, with older Mexican Americans the largest segment of US Hispanics (65%).21,36 Older Mexican Americans are unique for several reasons. First, they have the highest prevalence of diabetes, obesity, and disability, all risk factors associated with pain syndromes.1,14,27 Second, they have poor access to medical care for various conditions (eg, arthritis and diabetes) associated with pain.29 Third, the high level of low health literacy affects their ability to manage complex comorbidities in the face of a changing US health care system.37
Frailty is defined as “a physiologic state of increased vulnerability to stressors that results from decreased physiologic reserves, and even dysregulation, of multiple physiologic systems.”12 Frailty is highly prevalent in older adults and is associated with several adverse health outcomes, including disability, cognitive decline, institutionalization, and mortality.12 Research has shown pain as a risk factor for frailty among older adults.24,34,38–40 Most of these studies that have investigated the relationship between pain and frailty are of cross-sectional design7,34,38 or systematic reviews, with few longitudinal studies, mostly in non-Hispanic populations.24,31,39,40 For example, Megale and colleagues using participants from the Concord Health and Ageing in Men Project (CHAMP) found that, after 5 years, those with chronic pain were at 1.6 times greater risk of becoming frail than those without pain.24 Wade and colleagues using participants from the English Longitudinal Study of Ageing (ELSA) found that those with severe pain were 4 times more likely to become frail after 8 years of follow-up.40
Although previous studies show a relationship between pain and frailty, these studies were conducted mostly in men, non-Hispanic populations, and had less than 10-year follow-up. Little is known about the effect of pain and the long-term risk of becoming frail among older Mexican Americans, a population with high rates of frailty. Therefore, the objective of this study was to examine pain as a predictor of frailty over 18 years of follow-up among older Mexican Americans who were nonfrail at baseline.
2.1. Data source and study sample
The data came from the Hispanic Established Populations for the Epidemiological Study of the Elderly (EPESE), an ongoing longitudinal study of 3050 Mexican Americans aged 65 years and above residing in 5 Southwestern states of US Information of the Hispanic EPESE (survey instrument, definition of variables, and the deidentified raw data) are available at the National Archive of Computerized Data on Aging at the University of Michigan.25 This study used data collected from wave 2 (1995/96) to wave 8 (2012/13). The baseline interview information was used to assess weight loss (a component of the frailty phenotype) as the difference between weight measured in 1993 to 1994 (baseline) and weight measured in 1995 to 1996 (wave 2). Of the 2438 interviewed at wave 2 (hereafter referred as baseline), 974 (51.4%) were nonfrail, 622 (32.8%) prefrail, and 299 (15.8%) frail. We excluded 299 participants who were frail and 594 with missing information for any of the covariates. The final sample included 1545 older Mexican Americans aged ≥67 years (Fig. 1). Participants excluded from the study were significantly more likely to be older; to report a heart attack, stroke, cancer, or hip fracture; to have body mass index (BMI) mean of 24 kg/m2; to have a mean Mini-Mental State Examination (MMSE) score of ≤21; and to report one or more limitations in ADLs compared with participants included in the study. At the end of follow-up (2012/2013), 245 participants were reinterviewed in person, 82 through proxy, 15 refused to be reinterviewed, 134 were lost to follow-up, and 1069 were confirmed dead through the National Death Index and reports from relatives. Figure 1 shows the number of death and refused/lost to follow-up participants at each wave of interview. The study and all research protocols were approved by the Institutional Review Board.
Pain was assessed from the response to the question: “In the past month, have you experienced pain or discomfort when you stood or walked?” Responses were coded as “Yes” or “No” at each wave.
2.2.2. Modified frailty phenotype
Frailty was assessed based on the modified frailty phenotype described by Fried et al.12 because not all 8 waves of the Hispanic EPESE survey collected data on physical activity. The physical activity information was collected only at wave 2 because of a shift in the Hispanic EPESE study objectives over time. Four frailty items were used: unintentional weight loss of >10 pounds, weakness, exhaustion, and slowness.2
Sociodemographic variables included age, sex, marital status, and years of formal education. Medical conditions were assessed by self-reports of diabetes mellitus, heart attack, stroke, hypertension, arthritis, hip fracture, or cancer. Body mass index was calculated dividing weight in kilograms by height in meters squared (kg/m2). Cognitive function was assessed with the MMSE.6,11 Depressive symptoms were assessed with the Center for Epidemiologic Studies of Depression scale.30 Disability was assessed using 7 items from a modified version of the Katz ADL scale.17
2.3. Statistical analysis
χ2 and t test were used to describe the sample characteristics by pain. General Equation Estimation using the GENMOD procedure in SAS was used to estimate the odds ratio (OR) of becoming frail over time (per year of follow-up) as a function of pain, controlling for sociodemographics, medical conditions, cognitive function, BMI, depressive symptoms, and ADL disability. Except for education and sex, all variables were analyzed as time varying. Participants who were lost to follow-up, refused, or died were included in the study until their last interview date for the 18 years of follow-up. Additional analysis excluded those who were prefrail or frail at baseline. All analyses were performed using SAS, version 9.4 (SAS Institute, Inc, Cary, NC).
At baseline/wave 2 (n = 1545), the average age of the participants was 74.3 years (SD = 5.6), 58.4% were female, and 54.6% were married. The mean formal years of education was 5.0 (SD = 3.9), and the BMI mean was 28.1 (SD = 5.1). A total of 538 (34.8%) participants reported pain. The most prevalent medical conditions were hypertension (44.8%), arthritis (42.4%), and diabetes (26%). The prevalence of frailty among those with pain ranged from 24.4% in wave 3 to 41% in wave 8 (Fig. 2).
Table 1 presents the baseline descriptive characteristics of the sample by pain status of those who were not frail at baseline (n = 1545). Participants who reported pain were significantly more likely to be female (66%), to have higher BMI (29.3 kg/m2), to report more arthritis (74.4%), hypertension (52.8%), high depressive symptoms (13.8%), and ADL disability (4%) compared to those without pain.
Table 2 presents the results of the General Estimation Equation model of becoming frail over 18 years of follow-up as a function of pain, controlling for sociodemographics, comorbid conditions (diabetes mellitus, heart attack, stroke, hypertension, arthritis, hip fracture, and cancer), cognitive function, BMI, depressive symptoms, and ADL disability. Over time, the odds of becoming frail was 1.04 (95% confidence interval [CI] = 1.01-1.07). Participants reporting pain had 1.71 (95% CI = 1.41-2.09) higher odds of becoming frail over time after controlling for all covariates. Other factors associated with significantly higher odds of becoming frail were older age (OR = 1.05; 95% CI = 1.02-1.07), hip fracture (OR = 2.41; 95% CI = 1.29-4.49), high depressive symptoms (OR = 1.08; 95% CI = 1.06-1.09), and ADL disability (OR = 2.59; 95% CI = 2.06-3.25). Female participants (OR = 0.78; 95% CI = 0.62-0.97), those with higher levels of education (OR = 0.97; 95% CI = 0.95-0.99) and those with high MMSE score (OR = 0.98; 95% CI = 0.96-0.99), were less likely to become frail over time. When we excluded those who were prefrail or frail at baseline, the odds of becoming frail as a function of pain was 1.61 (95% CI = 1.26-2.08) after controlling for all covariates.
The current study examined whether pain in older Mexican Americans is a risk factor for frailty among those who were nonfrail at baseline. Our findings showed that those who reported pain were 1.7 times more likely to become frail over 18 years of follow-up, after controlling for all covariates. Older age, hip fracture, high depressive symptoms, and ADL disability were also associated with higher odds of becoming frail over time. Female participants, those with higher levels of education and those with a high MMSE score, were less likely to become frail over time.
The findings of this study are similar to those from the CHAMP and EMAS studies.24,39 Participants in the CHAMP study who reported pain were 1.6 times more likely to develop frailty over 2 years of follow-up.24 Participants in the EMAS study who reported some pain and those who reported chronic widespread pain were 1.5 and 4.3 times more likely, respectively, to become frail after 4 years of follow-up.39 However, our findings differ from those reported in the ELSA study, where those with moderate pain and severe pain were 3.1 and 3.8 times more likely, respectively, to become frail over time.40
Our study included several important differences from previous research examining the relationship between pain and frailty. We found that the percent of older Mexican Americans with pain-associated frailty increased from 24.4% in 1995/1996 to 41% in 2012/2013. This increase is concerning, and the reasons for it are unclear. This finding suggests a need to develop policies to increase access to culturally appropriate interventions for optimal management of common conditions (eg, diabetes, arthritis, and depression) associated with pain in this population. With the recent federal rule restricting prescribing of opioid analgesics, there is a need to facilitate access of those living with pain to evidence-based nonopioid modalities such as physical therapy, occupational therapy, joint injections, and integrative care.9 The most important difference between our study and previous reports is that ours includes a large population-based sample of older Mexican Americans, an underserved group with unique risk factors related to health care access, delivery, and outcomes in the US health care system.29 Our study involved a longer follow-up period (18 years) than previous investigations and included both male and female participants who were nonfrail at baseline.
The association between pain and frailty can be explained by mechanisms that underlie both conditions. It has been shown that pain is associated with weak grip strength,19 reduced gait speed,28 and malnutrition,5 all components of the frailty phenotype.12 Persistent pain acts as a stressor by triggering the stress mechanism and diminishing physiologic reserves, in turn increasing the risk of developing frailty.7,16,32 Previous studies have suggested that pain may lead to alterations in the hypothalamic–pituitary–adrenal axis and cellular inflammation that can potentially predisposes the individual to frailty.18,22 In addition, older adults are vulnerable to musculoskeletal pain due to progressive age-related pathological changes that impair their ability to cope with pain and eventually predisposes them to a greater risk of adverse health outcomes, comorbidities, functional impairment, disability, and frailty.4,26,41 Prevention and early treatment may reduce the burden of pain and potentially delay the onset of frailty in this population.
Our study has some limitations. First, pain and comorbid conditions were assessed through self-reports. This may lead to recall bias as compared to physician assessment. However, self-reported data for pain have been shown to be robust, particularly for dichotomous measures such as pain vs no pain.23 Second, not including the physical activity criterion as a part of the frailty phenotype measure could have underestimated the rate of frailty. Third, participants excluded from the study were less healthy compared to those included, which might have underestimated the relationship between pain and frailty. Fourth, the subjects who died before wave 2 may have produced a survival bias. Fifth, we do not have information on pain duration, pain intensity, or pain treatment. Finally, our findings are not generalizable to the larger Hispanic population in the United States. This study has several strengths, including its longitudinal design, the inclusion of sociodemographics and medical conditions as time varying, the length of follow-up, and a focus on a disadvantaged and underserved population.
In conclusion, our study establishes that nonfrail older Mexican Americans with pain are more likely to experience frailty over time than those without pain. This effect persisted after controlling for demographics and health characteristics. Our findings suggest that early assessment and proper management of pain may reduce frailty and improve the quality of life in this at-risk and underserved population.
Conflict of interest statement
The authors have no conflicts of interest to declare.
Supplemental video content
A video abstract accompanying this article can be found at http://links.lww.com/PAIN/A884.
This work was supported by the National Institute on Aging, the National Institute on Minority Health and Health Disparities, Texas Resource Center on Minority Aging Research, and the National Center for Medical Rehabilitation Research in the National Institute of Child Health and Human Development in the National Institutes of Health (R01 AG10939, R01 AG017638, 1P30 AG059301-01, K01 HD086290, and R01 MD010355). The authors acknowledge the assistance of Sarah Toombs Smith, PhD, ELS, in article preparation. Dr Toombs Smith received no compensation for this effort beyond her salary at the UTMB Sealy Center on Aging.
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